PXD028037-1

PXD028037 is an original dataset announced via ProteomeXchange.

Title	A lysosome-targeted DNA nanodevice selectively targets macrophages to attenuate tumors
Description	Activating CD8+ T cells by antigen cross-presentation is remarkably effective at eliminating tumors. Although this function is traditionally attributed to dendritic cells, tumor-associated macrophages (TAMs) can also cross-present antigens. TAMs are the most abundant tumor-infiltrating leukocyte. Yet, TAMs have not been leveraged to activate CD8+ T cells because mechanisms that modulate their ability to cross-present antigens are incompletely understood. Here we show that TAMs harbor hyperactive cysteine protease activity in their lysosomes which impedes antigen cross-presentation, thereby preventing CD8+ T cell activation. We developed a DNA nanodevice (E64-DNA) targeted to lysosomes of TAMs in mice. E64-DNA inhibits the population of cysteine proteases present specifically inside lysosomes of TAMs, improves their ability to cross-present antigens, and attenuates tumor growth via CD8+ T cells. When combined with cyclophosphamide, E64-DNA showed sustained tumor regression in a triple-negative-breast-cancer model. Our studies demonstrate that DNA nanodevices can be targeted with organelle-level precision to reprogram macrophages and achieve immunomodulation in vivo.
HostingRepository	PRIDE
AnnounceDate	2021-10-14
AnnouncementXML	Submission_2021-10-13_23:17:16.678.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tomas Vaisar
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-19 21:41:17	ID requested
⏵ 1	2021-10-13 23:17:17	announced

Dataset with its publication pending

submitter keyword: Macrophages, lysosomes, cysteine proteases, antigen cross-presentation, cancer, LC-MSMS

Lev Becker
contact affiliation	Ben May Department of Cancer Research, University of Chicago
contact email	levb@chicago.edu
lab head
Tomas Vaisar
contact affiliation	University of Washington
contact email	tvaisar@uw.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/10/PXD028037

PRIDE project URI

• PRIDE
  1. PXD028037
     1. Label: PRIDE project
     2. Name: A lysosome-targeted DNA nanodevice selectively targets macrophages to attenuate tumors